Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 137
Filtrar
1.
JSLS ; 25(1)2021.
Artigo em Inglês | MEDLINE | ID: mdl-33879996

RESUMO

Background and Objectives: This study was conducted to identify whether surgical stress during the peri-operative period of robot-assisted radical prostatectomy might affect biochemical recurrence in patients with positive surgical margins. Methods: Participants in the present study were 324 consecutive patients with localized prostate cancer who underwent robot-assisted radical prostatectomy between February 2013 and June 2018. Positive surgical margins were diagnosed in 61 of them. Patients with positive surgical margins were divided into those with (n = 19) and those without (n = 42) biochemical recurrence. Lymph node dissection, estimated blood loss, inhalation anesthetic volume, and surgical duration were evaluated as indicators of surgical stress. White blood cell count, C-reactive protein, body temperature, and usage of analgesics were postoperatively evaluated as surrogate markers of surgical stress. The associations between factors, including patients' characteristics and pathological features, and biochemical recurrence were investigated. Results: In univariate analyses, surgical duration (P = 0.004), D'Amico risk class (P = 0.002), Gleason score (P = 0.022) and the number of positive cores in prostate biopsy (P = 0.009) were statistically significantly associated with biochemical recurrence. In multivariate analyses, only surgical duration was significantly associated with biochemical recurrence (P = 0.042), at a cut-off value of surgical duration of 228.5 minutes. Conclusions: Prolonged surgical duration is associated with biochemical recurrence in patients with positive surgical margins. Thus, surgical duration should be limited as much as possible to reduce surgical stress, which might cause biochemical recurrence.

2.
Intern Med ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33642487

RESUMO

A 45-year-old man with allergic bronchopulmonary aspergillosis (ABPA) was treated with oral prednisolone (PSL) (30 mg/day), inhaled corticosteroids, and long-acting beta2-agonists. After confirmation of a PSL-dependent status (8 mg/day), subcutaneous injection with anti-interleukin (IL)-5 antibody (mepolizumab, 100 mg/month) was performed, and the PSL dose was tapered to 5 mg/day. However, ABPA recurred and proved refractory to oral itraconazole (200 mg/day). Alternative subcutaneous injection therapy with dupilumab (induction dose of 600 mg followed by a maintenance dose of 300 mg/2 weeks) enabled the successful withdrawal of oral PSL without clinical deterioration. This case demonstrates the potential utility of dupilumab for steroid-dependent ABPA via the synergistic suppression of IL-4 and IL-13 compared to monotherapy with anti-IL-5 antibody.

3.
Cancer Sci ; 112(5): 1899-1910, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33619826

RESUMO

Enzalutamide (Enz) is a second-generation androgen receptor (AR) antagonist for castration-resistant prostate cancer (CRPC) therapy, and it prolongs survival time in these patients. However, during Enz treatment, CRPC patients usually acquire resistance to Enz and often show cross-resistance to other AR signaling inhibitors. Although glucocorticoid receptor (GR) is involved in this resistance, the role of GR has not yet been clarified. Here, we report that chronic Enz treatment induced GR-mediated glucose transporter 4 (GLUT4) upregulation, and that upregulation was associated with resistance to Enz and other AR signaling inhibitors. Additionally, inhibition of GLUT4 suppressed cell proliferation in Enz-resistant prostate cancer cells, which recovered from Enz resistance and cross-resistance without changes in GR expression. Thus, a combination of Enz and a GLUT4 inhibitor could be useful in Enz-resistant CRPC patients.

4.
J Diabetes Complications ; 35(4): 107847, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33468395

RESUMO

AIMS: Whether or not renal structural changes, especially arteriolar hyalinosis, are related to the rate of renal functional decline and increase in urinary albumin excretion (UAE) at the early stage of diabetic nephropathy in patients with type 2 diabetes is still unknown. Our previous study determined that arteriolar hyalinosis is an independent risk factor for low GFR. We sought to determine whether arteriolar hyalinosis is also a risk factor for rapidly progressive decline in GFR. METHODS: We evaluated 22 type 2 diabetic patients with normo- or microalbuminuria who took part in the previous study, to clarify which renal histological factors were associated with changes in UAE and the glomerular filtration rate (GFR) during 11.0 ±â€¯3.0 years of follow-up. Light and electron microscopy-based morphometric analyses were performed to quantitatively evaluate the glomerular and interstitial structural changes. RESULTS: In all 22 patients, the GFR was significantly decreased from baseline to follow-up, while the UAE did not change markedly between the 2 periods. After 11 ±â€¯3 years of follow-up, the GFR was significantly lower in the rapid decliner group (annual rate of GFR decline ≥3.0%) than in the non-rapid decliner group (p = 0.017). The index of arteriolar hyalinosis (IAH) at baseline in the rapid decliners was significantly larger than in the non-rapid decliners (p = 0.015). The IAH showed a significant negative correlation with the GFR at follow-up (r = 0.50, p = 0.018) and the annual rate in the GFR decline (r = 0.47, p = 0.027) and significant positive correlations with UAE at follow-up (r = 0.46, p = 0.034) and the annual rate in the UAE increase (r = 0.57, p = 0.005). The GFR at follow-up in patients with IAH ≥2.0 was significantly decreased from baseline (p = 0.042) and significantly lower than that of the patients with IAH <2.0 (p = 0.026), which did not decrease significantly from baseline. The frequency of rapid decliners was larger in the IAH ≥2.0 than in the IAH <2.0 patients (p = 0.037). CONCLUSIONS: Aggravated arteriolar hyalinosis was a risk factor for a rapid GFR decline. This finding might reflect initial changes in early diabetic nephropathy.

5.
J Antimicrob Chemother ; 76(1): 189-198, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33035324

RESUMO

BACKGROUND: Baloxavir acid, the active form of the orally available prodrug baloxavir marboxil, is a novel cap-dependent endonuclease inhibitor of influenza virus. Baloxavir marboxil has been shown to rapidly reduce virus titres compared with oseltamivir in clinical studies. OBJECTIVES: We investigated the relationship between pharmacokinetic (PK) parameters and antiviral activity of baloxavir acid based on virus titre reduction in lungs of infected mice. METHODS: BALB/c mice infected with a sub-lethal dose of influenza A(H1N1), A(H1N1)pdm09, A(H3N2) or type B virus were treated on day 5 with oral baloxavir marboxil (0.5-50 mg/kg q12h), subcutaneous baloxavir acid (0.25-8 mg/kg/day), oseltamivir phosphate (5 or 50 eq mg/kg q12h) or other antivirals for 1 day. Lung virus titres were assessed 24 h after initial antiviral dosing. PK testing was performed at up to 24 h post-dosing of baloxavir marboxil or baloxavir acid in A/WSN/33-infected mice and the PK/pharmacodynamic (PD) relationship was evaluated for baloxavir acid. RESULTS: Oral baloxavir marboxil administration showed dose-dependent virus titre reductions in lungs of mice infected with the different types/subtypes of influenza viruses 24 h post-dosing. Baloxavir marboxil at 15 mg/kg q12h resulted in ≥100-fold and ≥10-fold reductions in influenza A and B virus titres, respectively, compared with oseltamivir phosphate. PK/PD analysis showed that the plasma concentration at the end of the dosing interval (Cτ) or the plasma concentration at 24 h after initial dosing (C24) was the PK parameter predicting the virus titres at 24 h post-dosing of baloxavir acid. CONCLUSIONS: PK/PD analysis of baloxavir acid based on virus titre reduction in this mouse model could be helpful in predicting and maximizing virological outcomes in clinical settings.

6.
Intern Med ; 60(3): 493-494, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33361682
7.
ChemMedChem ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230979

RESUMO

Acquired immunodeficiency syndrome (AIDS) is caused by infection with the human immunodeficiency virus (HIV). Although treatments against HIV infection are available, AIDS remains a serious disease that causes many deaths annually. Although a variety of anti-HIV drugs have been synthesized and marketed to treat HIV infected patients, nucleoside analogue reverse transcriptase inhibitors (NRTIs) that mimic nucleosides are used extensively and remain a subject of interest to medicinal chemists. However, HIV has acquired drug resistance against NRTIs and thus the struggle to find novel therapies continues. In this review, we trace the trajectory of NRTIs, focusing on the synthesis, mechanisms of action and applications of NRTIs that have been developed.

8.
PLoS One ; 15(10): e0240485, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33075060

RESUMO

During bronchoscopy, discomfort is mainly caused by an unavoidable cough; however, there are no reports of any predictive factors for strong cough during bronchoscopy identified before the procedure. To clarify the factors underlying the discomfort status and predictive factors for strong cough during bronchoscopy, we prospectively evaluated patients who underwent bronchoscopy at Kyorin University Hospital between March 2018 and July 2019. Before and after bronchoscopy, the enrolled patients answered a questionnaire regarding the procedure. At the same time, bronchoscopists evaluated cough severity using a four-grade cough scale. We evaluated patient characteristics and predictive factors associated with bronchoscopy from the perspective of discomfort and strong cough. A total of 172 patients were ultimately enrolled in this study. On multivariate logistic regression analysis, comparison of the subjective data between the discomfort and comfort groups revealed that factors that were more common in the former group were younger age (OR = 0.96, p = 0.002), less experienced bronchoscopist (OR = 2.08, p = 0.047), and elevation of cough score per 1 point (OR = 1.69, p < 0.001). Furthermore, the predictive factors for strong cough prior to performing bronchoscopy were female sex (OR = 2.57, p = 0.009), EBUS-TBNA (OR = 2.95, p = 0.004), and prolonged examination time of more than 36 min (OR = 2.32, p = 0.022). Regarding patients' discomfort, younger age, less experienced bronchoscopist, and the elevation of cough score per 1 point were important factors for discomfort in bronchoscopy. On the other hand, female sex, EBUS-TBNA, and prolonged examination time were crucial factors for strong cough.

9.
J Orthop Surg Res ; 15(1): 436, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32967710

RESUMO

BACKGROUND: Narrowing of the acromiohumeral distance (AHD) implies a rotator cuff tear. However, conventional AHD measurements using two-dimensional (2D) imaging or with the patient in the supine position might differ from that while standing during daily activity. This study aimed to evaluate the three-dimensional (3D) actual distance between the acromion and humeral head in the standing position and compare the AHD values with those obtained using conventional measuring methods. METHODS: Computed tomography (CT) images of 166 shoulders from 83 healthy volunteers (31 male and 52 female; mean age 40.1 ± 5.8 years; age range, 30-49 years) were prospectively acquired in the supine and standing positions using conventional and upright CT scanners, respectively. The minimum distance between the acromion and humeral head on the 3D surface models was considered as the 3D AHD. We measured the 2D AHD on anteroposterior digitally reconstructed radiographs. The AHD values were compared between the supine and standing positions and between the 2D and 3D measurements. RESULTS: The mean values of 2D AHD were 8.8 ± 1.3 mm (range, 5.9-15.4 mm) in the standing position and 8.1 ± 1.2 mm (range, 5.3-14.3 mm) in the supine position. The mean values of 3D AHD were 7.3 ± 1.4 mm (range, 4.7-14.0 mm) in the standing position and 6.6 ± 1.2 mm (range, 4.4-13.7 mm) in the supine position. The values of 3D AHD were significantly lower than those of 2D AHDs in both the standing and supine positions (P < 0.001). The values of 2D and 3D AHDs were significantly lower in the supine position than in the standing position (P < 0.001). CONCLUSIONS: This study evaluated the 3D AHD of normal shoulders in the standing position using an upright CT scanner. The present results indicated that assessments in the supine position can underestimate the value of the AHD compared with those made in the standing position and that assessments using 2D analysis can overestimate the value.

10.
J Orthop Surg Res ; 15(1): 411, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32933527

RESUMO

BACKGROUND: Although humans spend most of their day in a standing or sitting position, it is difficult to accurately evaluate the alignment of the shoulder girdle during daily activity, and its alignment changes between positions. The purpose of this study was to evaluate the 3-dimensional alignment of the shoulder girdle in the supine and standing positions by computed tomography (CT) and to assess the alignment changes of the shoulder girdle between these two positions. METHODS: CT scans of both shoulders of 100 healthy volunteers were prospectively taken in both supine and standing positions on the same day. The local 3-dimensional coordinate systems of the thorax, clavicle, and scapula were defined from the specific bony landmarks, and 3-dimensional angular rotations and positions of the clavicle and scapula were calculated. Differences in rotations and positions of the clavicle and scapula were evaluated between the supine and standing positions. RESULTS: Compared with the supine position, the clavicle showed significantly less elevation and greater retraction, and the scapula showed significantly less upward rotation, anterior tilting, and internal rotation in the standing position. Compared with the supine position, the clavicle center was located more inferiorly, posteriorly, and laterally, and the scapula center was located more inferiorly, posteriorly, and medially in the standing position. CONCLUSIONS: The present study showed that angular rotations and positions of the clavicle and scapula change significantly with position due to the effect of gravity.

11.
Inflamm Regen ; 40: 14, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32582401

RESUMO

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and the ensuing worldwide pandemic. The spread of the virus has had global effects such as activity restriction, economic stagnation, and collapse of healthcare infrastructure. Severe SARS-CoV-2 infection induces a cytokine storm, leading to acute respiratory distress syndrome (ARDS) and multiple organ failure, which are very serious health conditions and must be mitigated or resolved as soon as possible. Mesenchymal stem cells (MSCs) and their exosomes can affect immune cells by inducing anti-inflammatory macrophages, regulatory T and B cells, and regulatory dendritic cells, and can inactivate T cells. Hence, they are potential candidate agents for treatment of severe cases of COVID-19. In this review, we report the background of severe cases of COVID-19, basic aspects and mechanisms of action of MSCs and their exosomes, and discuss basic and clinical studies based on MSCs and exosomes for influenza-induced ARDS. Finally, we report the potential of MSC and exosome therapy in severe cases of COVID-19 in recently initiated or planned clinical trials of MSCs (33 trials) and exosomes (1 trial) registered in 13 countries on ClinicalTrials.gov.

12.
Lancet Infect Dis ; 20(10): 1204-1214, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32526195

RESUMO

BACKGROUND: Baloxavir marboxil (hereafter baloxavir), a selective inhibitor of influenza cap-dependent endonuclease, was approved in 2018 in the USA and Japan for the treatment of uncomplicated influenza in otherwise healthy individuals aged 12 years and older. We aimed to study the efficacy of baloxavir in outpatients at high risk of developing influenza-associated complications. METHODS: We did a double-blind, placebo-controlled and oseltamivir-controlled trial in outpatients aged 12 years and older in 551 sites in 17 countries and territories. Eligible patients had clinically diagnosed influenza-like illness, at least one risk factor for influenza-associated complications (eg, age older than 65 years), and a symptom duration of less than 48 h. Patients were stratified by baseline symptom score (≤14 vs ≥15), pre-existing and worsened symptoms at onset of illness compared with pre-influenza (yes or no), region (Asia, North America and Europe, or southern hemisphere), and weight (<80 kg vs ≥80 kg), and randomly assigned (1:1:1) via an interactive web-response system to either a single weight-based dose of baloxavir (40 mg for patients weighing <80 kg and 80 mg for patients weighing ≥80 kg; baloxavir group), oseltamivir 75 mg twice daily for 5 days (oseltamivir group), or matching placebo (placebo group). All patients, investigators, study personnel, and data analysts were masked to treatment assignment until database lock. The primary endpoint was time to improvement of influenza symptoms (TTIIS) in the modified intention-to-treat population, which included all patients who received at least one dose of study drug and had RT-PCR-confirmed influenza virus infection. Safety was assessed in all patients who receved at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT02949011. FINDINGS: 2184 patients were enrolled from Jan 11, 2017, to March 30, 2018, and randomly assigned to receive baloxavir (n=730), placebo (n=729), or oseltamivir (n=725). The modified intention-to-treat population included 1163 patients: 388 in the baloxavir group, 386 in the placebo group, and 389 in the oseltamivir group. 557 (48%) of 1163 patients had influenza A H3N2, 484 (42%) had influenza B, 80 (7%) had influenza A H1N1, 14 patients had a mixed infection, and 28 had infections with non-typable viruses. The median TTIIS was shorter in the baloxavir group (73·2 h [95% CI 67·2 to 85·1]) than in the placebo group (102·3 h [92·7 to 113·1]; difference 29·1 h [95% CI 14·6 to 42·8]; p<0·0001). The median TTIIS in the oseltamivir group was 81·0 h (95% CI 69·4 to 91·5), with a difference from the baloxavir group of 7·7 h (-7·9 to 22·7). Adverse events were reported in 183 (25%) of 730 patients in the baloxavir group, 216 (30%) of 727 in the placebo group, and 202 (28%) of 721 in the oseltamivir group. Serious adverse events were noted in five patients in the baloxavir group, nine patients in the placebo group, and eight patients in the oseltamivir group; one case each of hypertension and nausea in the placebo group and two cases of transaminase elevation in the oseltamivir group were considered to be treatment related. Polymerase acidic protein variants with Ile38Thr, Ile38Met, or Ile38Asn substitutions conferring reduced baloxavir susceptibility emerged in 15 (5%) of 290 baloxavir recipients assessed for amino acid substitutions in the virus. INTERPRETATION: Single-dose baloxavir has superior efficacy to placebo and similar efficacy to oseltamivir for ameliorating influenza symptoms in high-risk outpatients. The safety of baloxavir was comparable to placebo. This study supports early therapy for patients at high risk of complications of influenza to speed clinical recovery and reduce complications. FUNDING: Shionogi.


Assuntos
Antivirais/uso terapêutico , Influenza Humana/tratamento farmacológico , Oseltamivir/uso terapêutico , Oxazinas/uso terapêutico , Piridinas/uso terapêutico , Tiepinas/uso terapêutico , Triazinas/uso terapêutico , Adolescente , Adulto , Idoso , Antivirais/administração & dosagem , Criança , Dibenzotiepinas , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Morfolinas , Oxazinas/administração & dosagem , Piridinas/administração & dosagem , Piridonas , Tiepinas/administração & dosagem , Triazinas/administração & dosagem , Adulto Jovem
13.
Influenza Other Respir Viruses ; 14(6): 710-719, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32533654

RESUMO

BACKGROUND: Baloxavir marboxil (BXM), the oral prodrug of baloxavir acid (BXA), greatly reduces virus titers as well as influenza symptoms of uncomplicated influenza in patients. OBJECTIVES: To investigate the pharmacokinetic profiles of BXA and its efficacy against influenza A virus infection in ferrets. METHODS: Ferrets were dosed orally with BXM (10 and 30 mg/kg twice daily for 1 day), oseltamivir phosphate (OSP) (5 mg/kg twice daily for 2 days) or vehicle to measure the antiviral effects of BXM and OSP. The pharmacokinetic parameters of BXA was determined after single oral dosing of BXM. RESULTS: The maximum plasma concentrations of BXA were observed at 1.50 and 2.00 hours with the two BXM doses, which then declined with an elimination half-life of 6.91 and 4.44 hours, respectively. BXM at both doses remained detectable in the plasma in ferrets, which may be due to higher stability in liver microsomes. BXM (10 and 30 mg/kg twice daily) treatment at Day 1 post-infection (p.i.) reduced virus titers by ≥3 log10 of the 50% tissue culture infective doses by Day 2, which was significantly different compared with vehicle or OSP. Body temperature drops over time were significantly greater with BXM than with vehicle or OSP. Significant reduction in virus titers was also demonstrated when BXM was administrated after symptom onset at Day 2 p.i. compared with vehicle and OSP, although body temperature changes largely overlapped between Day 2 and Day 4. CONCLUSIONS: The results highlight the rapid antiviral action of BXM with post-exposure prophylaxis or therapeutic dosing in ferrets and offer support for further research on prevention of influenza virus infection and transmission.

14.
Menopause ; 27(8): 864-871, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32404795

RESUMO

OBJECTIVE: Ospemifene is a nonsteroidal selective estrogen receptor modulator (SERM) for the treatment of moderate symptomatic vulvar and vaginal atrophy (VVA) due to menopause. A postauthorization safety study is currently examining the incidence of venous thromboembolism (VTE) among postmenopausal women receiving ospemifene or other SERM (raloxifene, bazedoxifene, or tamoxifen, for noncancer indications), or with untreated VVA. METHODS: This interim analysis used the US MarketScan Commercial and Medicare Supplemental claims database from 2013 to 2017 to identify incident VTE. The incidence rate and 95% confidence interval of VTE during the first continuous course of treatment (or continuous untreated time for the untreated cohort) were calculated for each cohort overall and by age group, with sensitivity analyses examining incidence in the short term (up to 90 days) and long term (all available follow-up, regardless of treatment changes). RESULTS: Analyses included 8,188 ospemifene users, 11,777 other SERM users, and 220,242 women with untreated VVA. The incidence per 1,000 person-years and 95% confidence interval of VTE were 3.7 (1.7-7.1) for ospemifene, 11.5 (8.9-14.6) for other SERM, and 11.3 (10.8-11.7) for untreated VVA. Stratification by age and altering the time frame for analysis produced results with similar patterns to the primary analysis. CONCLUSIONS: This interim analysis of an ongoing study suggests a favorable safety profile for ospemifene with respect to VTE. Comparative analyses with covariate adjustment will be performed when data accrual is complete.

15.
Sci Rep ; 10(1): 4798, 2020 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-32179769

RESUMO

Protein overexpression sometimes causes cellular defects, although the underlying mechanism is still unknown. A protein's expression limit, which triggers cellular defects, is a useful indication of the underlying mechanism. In this study, we developed an experimental method of estimating the expression limits of target proteins in the human embryonic kidney cell line HEK293 by measuring the proteins' expression levels in cells that survived after the high-copy introduction of plasmid DNA by which the proteins were expressed under a strong cytomegalovirus promoter. The expression limits of nonfluorescent target proteins were indirectly estimated by measuring the levels of green fluorescent protein (GFP) connected to the target proteins with the self-cleaving sequence P2A. The expression limit of a model GFP was ~5.0% of the total protein, and sustained GFP overexpression caused cell death. The expression limits of GFPs with mitochondria-targeting signals and endoplasmic reticulum localization signals were 1.6% and 0.38%, respectively. The expression limits of four proteins involved in vesicular trafficking were far lower compared to a red fluorescent protein. The protein expression limit estimation method developed will be valuable for defining toxic proteins and consequences of protein overexpression.

16.
Front Nutr ; 7: 5, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32175325

RESUMO

Cancer cachexia is highly prevalent in patients with progressive cancer and is characterized by decreased food consumption, and body weight. Japanese herbal medicine Ninjinyoeito (NYT), composed of 12 herbal crude drugs, is prescribed in Asian countries to improve several symptoms such as anorexia and fatigue, which are commonly observed in patients with cancer cachexia. However, the action mechanisms of NYT in improving anorexia or fatigue in patients with cancer are not clear. Therefore, in the present study, we examined the effects of NYT on the activities of several G-protein-coupled receptors (GPCRs), which activate hyperphagia signaling in the central nervous system, using an in vitro assay with the CellKey™ system, which detects the activation of GPCRs as a change in intracellular impedance (ΔZ). NYT increased the ΔZ of human embryonic kidney 293 (HEK293) cells expressing orexin 1 receptor (OX1R) and those expressing neuropeptide Y1 receptor (NPY1R) in a dose-dependent manner. On the contrary, NYT did not significantly increase the ΔZ of HEK293A cells expressing growth hormone secretagogue receptor (GHSR) and those expressing NPY5R. The selective OX1R antagonist SB674042 significantly decreased the NYT-induced increase in ΔZ in OX1R-expressing cells. Contrarily, the selective NPY1R antagonist BIBO3340 failed to inhibit the NPY-induced increase in ΔZ in NPY1R-expressing cells. Additionally, we prepared modified NYT excluding each one of the 12 herbal crude drugs in NYT and investigated the effects on the activity of OX1R. Among the 12 modified NYT formulations, the one without citrus unshiu peel failed to activate OX1R. A screening of each of the 12 herbal crude drugs showed that citrus unshiu peel significantly activated OX1R, which was significantly suppressed by SB674042. These finding suggest that NYT and citrus unshiu peel could increase food intake via activation of orexigenic OX1R-expressing neurons in the hypothalamus. This study provides scientific evidence to support the potential of NYT for cancer patients with anorexia.

17.
PLoS One ; 15(2): e0229238, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32106233

RESUMO

BACKGROUND: Airway obstruction due to decreased airway diameter and increased incidence of mucus plugs has not been directly observed in asthma exacerbation. We studied the changes in the inner diameter of the airway (Din) and the frequency of mucus plugs by airway generation in patients with asthma exacerbation. We compared these patients to those in a stable phase using high-resolution computed tomography (HRCT). METHODS AND FINDINGS: Thirteen patients with asthma were studied by HRCT during asthma exacerbation and in a stable period. The HRCT study was performed on patients who could safely hold their breath for a short while in a supine position 1 hour after initial treatment for asthma exacerbation. Using a curved multiplanar reconstruction (MPR) software, we reconstructed the longitudinal airway images and the images exactly perpendicular to the airway axis to measure the Din and mucus plugs from the second- (segmental) to sixth-generation bronchi in all segments of the lungs.The ratios of Din (exacerbation/stable) were 0.91(P = 0.016), 0.88 (P = 0.002), 0.83 (P = 0.001), 0.80 (P = 0.001), and 0.87 (NS) in the second-, third-, fourth-, fifth-, and sixth-generation bronchi, respectively. The percentages of airway obstruction due to mucus plugs were notably higher in the fourth- and fifth-generation bronchi (17.9%/18.1% in stable phase and 43.2%/45.9% in the exacerbation phase, respectively) than in the other generations of bronchi. CONCLUSIONS: Among the bronchi examined, the fourth- and fifth-generation bronchi were significantly obstructed during asthma exacerbation compared with the stable phase in terms of a decreased airway diameter and mucus plugs.


Assuntos
Obstrução das Vias Respiratórias/etiologia , Asma/complicações , Brônquios/patologia , Muco/metabolismo , Obstrução das Vias Respiratórias/diagnóstico por imagem , Obstrução das Vias Respiratórias/patologia , Asma/diagnóstico por imagem , Brônquios/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Muco/química , Muco/diagnóstico por imagem , Prognóstico , Tomografia Computadorizada por Raios X/métodos
18.
J Med Case Rep ; 13(1): 355, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31796112

RESUMO

BACKGROUND: Traumatic hemipelvectomy is a catastrophic fracture of the pelvis as a result of high-energy trauma, such as in a car accident. There have been few case reports of traumatic hemipelvectomy because many of these patients die before they are transferred to a hospital. However, an increasing number of patients are being saved and admitted to hospital due to improvements in resuscitation and the emergency response system. Accordingly, there has been a growing body of reports on the management and reconstruction of traumatic hemipelvectomy. CASE PRESENTATION: A healthy 20-year-old Japanese man was trapped beneath a 3-ton steel frame while working on a crane. We describe here a very challenging case of traumatically induced bilateral partial hemipelvectomy with successful reconstruction of our patient's pelvis using a unilateral anterolateral thigh flap. CONCLUSION: To the best of our knowledge, there have been few reports of bilateral hemipelvectomy and our case is the first to be successfully treated with a unilateral anterolateral thigh flap.


Assuntos
Hemipelvectomia/efeitos adversos , Traumatismo Múltiplo/cirurgia , Pelve/lesões , Pelve/cirurgia , Procedimentos Cirúrgicos Reconstrutivos , Retalhos Cirúrgicos , Acidentes de Trabalho , Indústria da Construção , Humanos , Japão , Masculino , Adulto Jovem
19.
BMC Dev Biol ; 19(1): 24, 2019 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-31864287

RESUMO

BACKGROUND: Tardigrades are microscopic organisms, famous for their tolerance against extreme environments. The establishment of rearing systems of multiple species has allowed for comparison of tardigrade physiology, in particular in embryogenesis. Interestingly, in-lab cultures of limnic species showed smaller variation in hatching timing than terrestrial species, suggesting a hatching regulation mechanism acquired by adaptation to their habitat. RESULTS: To this end, we screened for coordinated gene expression during the development of two species of tardigrades, Hypsibius exemplaris and Ramazzottius varieornatus, and observed induction of the arthropod molting pathway. Exposure of ecdysteroids and juvenile hormone analog affected egg hatching but not embryonic development in only the limnic H. exemplaris. CONCLUSION: These observations suggest a hatching regulation mechanism by the molting pathway in H. exemplaris.


Assuntos
Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Tardígrados/fisiologia , Animais , Regulação da Expressão Gênica no Desenvolvimento , Muda , Análise de Sequência de RNA , Tardígrados/genética , Tardígrados/crescimento & desenvolvimento
20.
Bioconjug Chem ; 30(12): 3028-3037, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31738536

RESUMO

Mucosal vaccination, which secretion of immunoglobulin A (IgA) on the mucosa is accompanied by induction of immunoglobulin G (IgG) in the blood, is one of the most effective ways to circumvent influenza epidemics caused by incorrect prediction of epidemic viral strains or viral mutation. Secreted IgA is expected to prevent hosts from being infected with heterologous viruses because this antibody cross-reacts to strains other than those used for immunization. Our previous mouse experiments revealed that intranasal IgA with cross-reactivity was induced through nasal inoculation with inactivated whole viral particles of the H1N1 A/New Caledonia/20/99 IVR116 (NCL) strain in the presence of hyaluronic acid modified with tetraglycine-l-octaarginine. In the present study, heterologous influenza virus challenge was performed to validate a potential of the hyaluronic acid derivative as a mucosal adjuvant with cross-protective abilities. Serious weight loss was observed when mice were nasally inoculated with inactivated NCL viruses alone and subsequently exposed to mouse-adapted infectious viruses of the H1N1 A/Puerto Rico/8/34 (PR8) strain. The symptom associated with virus infection was hardly ever observed for mice inoculated with a mixture of the viral antigens and tetraglycine-l-octaarginine-linked hyaluronic acid, presumably due to high induction of IgG and IgA capable of cross-reacting to PR8 viruses. Less proliferation of PR8 viruses in those mice was also supported by an insignificant elevation of antibody levels through virus exposure. Our polysaccharide derivative enabled hosts to acquire adaptive immunity with cross-protective abilities against heterologous virus infection.


Assuntos
Adjuvantes Imunológicos/química , Reações Cruzadas/imunologia , Ácido Hialurônico/farmacologia , Vacinas contra Influenza/química , Influenza Humana/prevenção & controle , Influenzavirus A/imunologia , Adjuvantes Imunológicos/farmacologia , Administração Intranasal , Animais , Humanos , Ácido Hialurônico/química , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Vírus da Influenza A Subtipo H1N1/imunologia , Camundongos , Oligopeptídeos/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...